Lymphoma Found to Be Genetically Linked to Diamond-Blackfan Anemia

Lymphoma Found to Be Genetically Linked to Diamond-Blackfan Anemia

Researchers at the Spanish National Cancer Research Centre (CNIO) have uncovered the genetic link between Diamond-Blackfan anemia (DBA) and cancer predisposition, in particular to lymphoma. The research paper, entitled “Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis,” was published in Cell Reports.

DBA patients, in addition to suffering from a rare form of anemia, also present a predisposition to cancer development, namely lymphomas and solid tumors, such as osteosarcoma and colon cancer. DBA is caused by a malfunction in the bone marrow that results in a failure to produce sufficient red blood cells, eventually leading to the development of anemia.

Ribosomal proteins are part of ribosomes, structures responsible for protein biosynthesis inside cells. DBA patients have mutations in several ribosomal proteins, a fact that has led to extensive research into these molecules. Until now, investigators have tried to connect the dysfunctional ribosomal proteins present in patients to their predisposition to cancer without much success. In this mice study, inhibition of RPL11 was linked to DBA and to oncogenic pathways, with RPL11 deficiency found to originate a decrease in the expression of the tumor suppressor gene p53.

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Lead researcher Dr. Manuel Serrano commented on this finding and why his group focused on RPL11: “Cells need the ribosomes to function properly in order to proliferate and grow; we knew that when something goes wrong in these organelles, RPL11 operates as a switch that activates the p53 gene to stop the cells from proliferating and forming tumours; this mechanism is called ribosomal stress. P53 is one of the main tumour suppressor genes identified to date, to the extent that its relevance in preventing cancer has led to it being named the guardian of the genome. This important function made us think that the protein could play a crucial role in the cancer predisposition observed in patients with DBA: if RPL11 is mutated, it loses the ability to activate p53 to prevent tumors caused by cellular damage.” Furthermore, mutations in this protein also lead to the upregulation of oncogene MYC, therefore promoting the development of tumors.

Researchers are now investigating if these findings can be translated to human patients. Current treatments focus on relieving symptoms of anemia, by blood transfusions, corticosteroisds and bone marrow transplants. This research might lead to therapies that not only increase red blood cells, but also address the higher risk of cancer development among DBA patients.

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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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